1-(3,4-Dichlorobenzyl)-5-octylbiguanide represented by Formula (1)
(hereinafter sometimes referred to simply as “Compound A”) and salts thereof are compounds with high antimicrobial activity. Therefore, microbicides containing these compounds as active ingredients are being studied.
Compound A has heretofore been produced by the process disclosed in Japanese Unexamined Patent Publication No. H5-194361.
Specifically, the publication discloses a process in which a compound represented by Formula (2)
is reacted with a compound represented by Formula (3)
to produce Compound A.
In the process disclosed in the publication, the reaction of Compound (2) with Compound (3) is carried out in the presence or absence of a solvent such as 2-ethoxyethanol, 2-methoxyethanol, o-dichlorobenzene, mesitylene, or the like.
However, of the above solvents, 2-ethoxyethanol, 2-methoxyethanol, and o-dichlorobenzene have undesirable properties, such as positivity in chromosome tests, mutagenicity, teratogenicity, etc., and are not suitable as solvents for use in the production of medicines. o-Dichlorobenzene also has the problem of a high boiling point. 2-Ethoxyethanol, 2-methoxyethanol, and o-dichlorobenzene cannot therefore be used in the industrial production of Compound A. Thus, in the above publication, of the above solvents, only mesitylene is specifically used in the Examples.
Example 1 of the above publication specifically describes a process in which Compound (2) and a hydrochloride of Compound (3) are heated under reflux using mesitylene as a solvent, to thereby produce a monohydrochloride of Compound A. However, the yield of the process is as low as 53.1% based on Compound (2), and as low as 56.9% based on the hydrochloride of Compound (3), and is far from satisfactory. Further, since the reaction is carried out at the boiling point of mesitylene, i.e., at a high temperature of 162 to 164° C., a special heater is necessary, and it is very difficult to perform the reaction on an industrial scale using general-purpose equipment.
Thus, the above-mentioned known process is not capable of producing Compound A on an industrial scale.